Morning Sickness Tx Better if Started Before Symptoms

Action Points

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

In this randomized study in pregnant women who had a history of severe nausea and vomiting of pregnancy, preemptive treatment significantly decreased the risk of hyperemesis gravidarum and increased the likelihood of symptom control compared with institution of treatment with onset of symptoms.

Preemptive treatment starting at recognition of pregnancy using a combination of vitamin B6 and the antihistamine doxylamine reduced the incidence of severe nausea and vomiting in the first 3 weeks of symptoms by 70% compared with the same combination drug started at the first sign of symptoms (P<0.04).

The prophylactic strategy also significantly cut down on the most serious manifestation, hyperemesis gravidarum, Caroline Maltepe, BA, coordinator for the help line at the Hospital for Sick Children in Toronto, reported here at the Society for Maternal-Fetal Medicine meeting. Hyperemesis gravidarum is the condition that hospitalized Kate Middleton, Duchess of Cambridge and wife of Britain's Prince William, in December.

The combination drug is known as Diclectin in Canada, where it is the only anti-emetic approved for use in pregnancy. It was on the U.S. market as Bendectin until the early 198os, when a host of lawsuits over birth defects led to its voluntary withdrawal.

The strategy would likely generalize to other medications U.S. physicians commonly use for hyperemesis, suggested session co-chair Robert Silver, MD, chief of maternal-fetal medicine at the University of Utah in Salt Lake City.

Although most of these medications are "quite safe," clinicians should wait for the studies to be done to show the risk-to-benefit ratio of preemptive administration for the general population, he told MedPage Today in an interview.

However, "if patients are at extremely high risk -- if they've had really bad hyperemesis before -- it's a very reasonable strategy to try preemptive treatment, because we're not very good at taking care of this problem," he added. "None of the medications work in all of the patients all of the time."

Maltepe pointed to a prior small nonrandomized trial from her group showing that physicians' choice of any anti-emetic medication given preemptively was better for reducing recurrence of hyperemesis gravidarum and severity of symptoms.

The new prospective study enrolled 59 women who called in to a morning sickness help line hosted by the Hospital for Sick Kids and sponsored, in part, by Duchesnay, the maker of Diclectin. The company also sponsored the trial.

Women who indicated at a detailed intake interview that they had had severe nausea and vomiting in their last pregnancy were randomized to start taking the anti-emetic upon recognition of their pregnancy but before morning sickness symptoms began or to start the drug only when symptoms began.

Both groups received the same intensive counseling on evidence-based hyperemesis management guidelines. Drug doses, follow-up contacts, and other characteristics were similar between groups as well.

All women in both groups did develop nausea and vomiting symptoms.

But fewer pre-emptive group patients reached the moderate-to-severe level during the first 3 weeks of symptoms, which Maltepe noted is typically when severity peaks.

The prevalence of scores of 11 or higher on the aptly-named PUQE scale during that period was 15% compared with 39% among the controls who started on the anti-emetic at symptom onset (P<0.04).

Symptoms resolved earlier in the pregnancy with prophylaxis as well, at a median of 26 weeks gestation compared with 33 weeks, although this was not a significant difference at P=0.18.

Prevalence of hyperemesis gravidarum was lower in both groups than in the prior pregnancy, but by an absolute 43 percentage points with preemptive treatment versus 16 percentage points with the usual strategy of administration (P=0.047).

Maltepe noted that these benefits were atop the dietary and lifestyle strategies women were counseled on as well as other pharmacological and nonpharmacological approaches.

"By doing all that, we do improve maternal quality of life," Maltepe told the audience.

The audience, though, wasn't so generous during the question and answer period, criticizing the study on the lack of a placebo-controlled or other active drug comparator arm as well as the industry link to the help line and even the possibility that the effect seen wasn't real.

"By introducing knowledge of what they were getting in a disease that's heavily influenced by psychosocial factors ..." he trailed off. "It's unethical to promote this kind of industry-funded study based on this kind of study design."

The next question at the microphone also brought up conflict of interest issues from a single industry sponsor for the help line, although Maltepe countered that the advice the help line gives is based on guidelines with an algorithm that freely makes use of non-vitamin B6/doxylamine strategies as well.

The trial does include a third comparator arm of women who had severe nausea and vomiting or hyperemesis gravidarum in a prior pregnancy but didn't consent to participate in the trial.

Comparison among the three groups will be reported later, along with the trial's primary endpoint of severe symptoms marked by a PUQE score of 13 or higher or hyperemesis gravidarum, Maltepe explained in an interview.

She acknowledged the small sample size and that further larger studies are warranted.

"It would be of great interest to compare this medication to other medications," Silver agreed.

The study was sponsored by the Hospital for Sick Children and Duchesnay.

Maltepe reported having no conflicts of interest.

Silver reported having no conflicts of interest to disclose.

Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

MedPageToday is a trusted and reliable source for clinical and policy coverage that directly affects the lives and practices of health care professionals.

Physicians and other healthcare professionals may also receive Continuing Medical Education (CME) and Continuing Education (CE) credits at no cost for participating in MedPage Today-hosted educational activities.